POS1083 INCREASED INTESTINAL PERMEABILITY IN PATIENTS WITH PSORIATIC ARTHRITIS CLASSIFIED AS TREATMENT FAILURES DURING THE 26-WEEK FLORA TRIAL
Authors: M. Skov Kragsnaes, J. Miguens Blanco, E. Chekmeneva, A. Salam, M. R. Lewis, J. Kjeldsen, H. C. Horn, H. L. Munk, J. K. Pedersen, J. Marchesi, T. Ellingsen
Journal: Annals of the Rheumatic Diseases (2022)

Background Changes in the integrity of the intestinal wall may be implicated in the gut-joint axis of inflammatory arthritis. 1 Yet, the gut barrier is only poorly evaluated in psoriatic arthritis (PsA). 2 Objectives In this exploratory study, we evaluated intestinal permeability before and 26 weeks after one faecal microbiota transplantation (FMT) or sham intervention in adults with PsA. Methods We have previously reported the clinical results of a 26-week, double-blind, parallel-group, 1:1 randomised, sham-controlled, superiority trial of gastroscopic-guided FMT as an add-on treatment to methotrexate in 31 adults with active peripheral PsA (FLORA trial, NCT03058900 ). 3 The primary efficacy endpoint was the proportion of participants who experienced treatment failure through 26 weeks, defined as need for more than one intra-articular glucocorticoid injection and/or anti-TNFα inhibition. We encouraged patients not to take nonsteroidal anti-inflammatory drugs during the trial. The FMT material was obtained from one of four healthy blood donors. As part of the trial, we performed a lactulose and mannitol test (L:M test) at baseline (n=31) and at the final 26-week visit (n=26) to assess the permeability of the intestinal wall (higher L:M ratios indicate higher permeability). After an overnight fasting, patients provided a urine sample before ingesting 10 g of lactulose and 5 g of D-mannitol. Samples were collected after 3 hours and stored at −80°C until analysis. No food or drinking (except for water) was allowed during the test. We measured the lactulose-to-mannitol ratio in the urine samples using a Waters Acquity UPLC system coupled to a high-resolution mass spectrometer Waters Xevo G2 QToF (Waters Corp., Milford, MA, USA). MassLynx software (Waters Corporation) was used for data acquisition and visual inspection. We used StataSE-64 to perform the Wilcoxon rank sum and the matched-pairs signed-rank test. Data is presented as median and range. The level of significance was set to 0.05. Results At baseline, no significant difference was observed in the L:M ratio between donors (n=4) and patients (n=31) (0.0065 [0–0.063] vs 0.014 [0–0.28]; p=0.50). The L:M ratio increased from baseline to week 26 in both the FMT (0.0020 [-0.27 – 0.32] and the sham group (0.0046 [-0.012 – 0.088]), but only in the sham group differed the baseline L:M ratio significantly from the one measured at week 26 (p=0.92 [FMT] and p=0.032 [sham]). The patients who were classified as treatment failures during the trial (n=7) had a significantly higher L:M ratio at week 26 compared to the patients who were non-failures (n=19) (0.027 [0.017 – 0.33]) vs 0.012 [0 – 0.064], p=0.01), please see Figure 1. Figure 1. L:M ratios at week 26 in treatment failures (n=7) and non-failures (n=19), respectively. Higher L:M ratios indicate higher intestinal permeability. Conclusion In the FLORA trial, intestinal permeability evaluated by the L:M test did not differ significantly between donors and patients at baseline. Whether the higher intestinal permeability observed in patients classified as treatment failures compared to non-failures at week 26 can be attributed to differences in disease activity and/or the instigation of additional immunosuppression in the failure group during the trial needs further investigation. References [1]Gracey E, Vereecke L, McGovern D, et al. Revisiting the gut-joint axis: links between gut inflammation and spondyloarthritis. Nat Rev Rheumatol . 2020;16(8):415-433. [2]Hecquet S, Totoson P, Martin H, et al. Intestinal permeability in spondyloarthritis and rheumatoid arthritis: A systematic review of the literature. Semin Arthritis Rheum . 2021;51(4):712-718. [3]Kragsnaes MS, Kjeldsen J, Horn HC, et al. Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial. Ann Rheum Dis . 2021;80(9):1158-1167. Disclosure of Interests None declared